The effects of antipsychotics on behavioral abnormalities of the Gunn rat (unconjugated hyperbilirubinemia rat), a rat model of schizophrenia

BackgroundThere have been reports of a positive relationship between schizophrenia and hyperbilirubinemia. Patients with schizophrenia show a significantly higher frequency of hyperbilirubinemia than patients suffering from other psychiatric disorders and when compared to the general population. Previously we observed that patients suffering from schizophrenia frequently present an elevated unconjugated bilirubin plasma concentration, when admitted to the hospital. In addition it was recently reported that unconjugated bilirubin exhibited neurotoxicity in the developing nervous system. We also reported that Gunn rats, which tend to show a high frequency of hyperbilirubinemia, may be used as an animal model of schizophrenia. In the present study, we assessed the effects of antipsychotics on Gunn rat behavioral abnormalities.MethodsWe examined the behavior of Gunn rats after treatment with risperidone (0.1 mg/kg), haloperidol (0.2 mg/kg), or aripiprazole (0.4 mg/kg) using an open-field test, social interaction test and a prepulse inhibition (PPI) test.ResultsThe administration of antipsychotics alleviated behavioral abnormalities, mimicking some positive and negative symptoms and cognitive defects of schizophrenia. The pharmacological reaction of Gunn rats to antipsychotics echoes the pharmacological response of humans to such antipsychotics.ConclusionsOur study suggested that the Gunn rat may be useful as a preclinical model of schizophrenia with which to evaluate the pharmacological properties of antipsychotics. The results obtained to date have been encouraging and warrant further research.

► Gunn rats demonstrated behavioral abnormalities similar to schizophrenia patients.
► Gunn rat's behavioral abnormalities decreased after administrating antipsychotics.
► The reaction of Gunn rats to antipsychotics mimics the response of humans.
► Gunn rats may provide a useful preclinical model of schizophrenia.